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TREATMENT AGENT FOR COGNITIVE DISORDERS, INDUCED BY AMYLOID β-PROTEIN, THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE, AND TREATMENT METHOD AND PATHOLOGICAL ANALYSIS METHOD RELATED TO THESE UPDATE

外国特許コード F150008246
掲載日 2015年3月27日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2014JP060665
国際公開番号 WO 2014171434
国際出願日 平成26年4月15日(2014.4.15)
国際公開日 平成26年10月23日(2014.10.23)
優先権データ
  • 特願2013-088319 (2013.4.19) JP
発明の名称 (英語) TREATMENT AGENT FOR COGNITIVE DISORDERS, INDUCED BY AMYLOID β-PROTEIN, THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE, AND TREATMENT METHOD AND PATHOLOGICAL ANALYSIS METHOD RELATED TO THESE UPDATE
発明の概要(英語) The present invention addresses the issue of providing an anti-Alzheimer's agent that uses an amyloid β-protein as the mechanism of action therefor but that is different from conventional mechanisms of action. This therapeutic agent for Alzheimer's disease contains a cognitive disorder treatment agent induced by an amyloid β-protein containing a peptide comprising an amino acid sequence indicated by SEQ ID NO. 1, or a peptide similar to same, in particular a peptide including an amino acid sequence indicated by SEQ ID NO. 2 being a partial sequence of SEQ ID NO. 1; and is characterized by containing said treatment agent. SEQ ID NO. 1: VLSSQQFLHRGHQPPPEMAGHSLASSHRNSMIPSAAT; SEQ ID NO. 2: HRGHQPPPEMA
従来技術、競合技術の概要(英語) BACKGROUND ART
Alzheimer's disease, cognitive decline (or remembering) the main condition that neurological disease. In particular in elderly is even though the predilection, there is no effective therapeutic, are worn out in aging society and the serious problem in developed countries. In the postmortem brain of Alzheimer's disease patients which neuritic plaques observed, this is' amyloid β protein ' aggregates with are known. Then, the amyloid β protein is the main cause of Alzheimer's disease is, by numerous studies in the widely accepted.
Amyloid β protein, a precursor thereof 'the amyloid precursor protein' generated from. The amyloid precursor protein and, on neural cell membranes is a membrane protein. In the normal brain, its extracellular domain α secretase, γ-secretase in the cell membrane and then are cut in the domain, the peptide is referred to as p3 outside of the cell production, is released. This is' non-amyloid generation path ' known as, amyloid β protein is not generated (non-patent document 1). In the normal brain, but the extracellular domain of the β-secretase is several % to truncated, extracellular amyloid β protein are secreted. However, in the brain Alzheimer's disease, amyloid β production amount of the protein will be increased, the aggregation of amyloid β protein species of high so as to produce are considered. Amyloid β protein with this property, finally Alzheimer's disease patients of senile plaques formed (amyloid aggregates), deposition is observed in the brain.
Amyloid β protein is found to have a cut, gradually aggregated, finally senile plaques (amyloid aggregates) are formed, agglomeration processes' oligomeric forms (amyloid β protein that associated with the several) ' in, known to be strong neurotoxicity. Amyloid β protein is in oligomeric forms, memory, learning of the neural phenomenon essential to inhibit synaptic plasticity, in vitro, both in vivo have been reported (non-patent document 2, 3). In addition, this oligomer administered to the body in the mouse brain, storage, can be lost to the learning ability have been reported (non-patent document 4, 5). A recent study, and the oligomeric forms of long-term exposure, and the like can also occur in neuronal cell death has been reported (non-patent document 6), to cause the onset of Alzheimer's disease has been paid attention as a substance.
In this way, as the cause of the amyloid β protein Alzheimer's disease is widely recognized that regardless of the fact that, currently clinically used in the therapeutic agent is Alzheimer's disease, amyloid β protein in such a manner that this design is not. Specifically, used as a therapeutic agent Alzheimer's disease (Patent Document 1) memantine or donepezil (Patent Document 2) is, and the acetylcholinesterase inhibitor respectively act as NMDA receptor inhibitors, amyloid β protein does not interact with. Since the agent is a so-called address, a dramatic improvement in the effect for Alzheimer's disease is at present.
In response to such a background, based on the mechanism of action (amyloid protein) new Alzheimer's development of therapeutics has been promoted. 1 Is one, the amyloid precursor protein from the production of amyloid β protein and attempted to attempt, the development of secretase control agent (non-patent document 1). Among them, development of γ secretase inhibitors and the most advanced, Begacestat Semagacestat (Patent Document 3) or the like (Patent Document 4), efforts have been performed and the clinical development. Another has attracted attention as a therapy is, amyloid β protein in the brain is removed and antibody-recognized, antibody therapy. Actually, solanezumab Bapineuzumab (Patent Document 5) or the like, this method has been developed for clinical history is.
However, with the center of the present development of amyloid protein Alzheimer's mechanism of action and there are problems that the therapeutic agent may be known. With respect to the γ secretase inhibitors, γ secretase substrates in the first place as well as the amyloid precursor protein, are known to be near about 100 (non-patent document 7). And includes an, important cell differentiation which may include Notch receptor (non-patent document 8), concern about side effects. Actually, was a strong candidate for the γ secretase inhibitors as Semagacestat is, developed in the year 2010 the third phase clinical trials are terminated. Anti-amyloid β antibody for the antibody therapy, vasculitis and vascular cerebral edema and the like which can occur, in fact, is promising as a therapeutic agent was also Bapineuzumab antibody, was developed in 2012 is stopped.
In addition, the stroma of the γ secretase is, cut the extracellular domain of the amyloid peptide may be ejected in some known (non-patent document 9, 10). These peptides are indicative of the activity since the γ secretase, fragment was cut to a biomarker of the invention of the Alzheimer's disease are some (Patent Document 6, 7). Also, referred to as Alcadein-β is membrane protein in vivo, cleaved by γ-secretase, by may be cut by further α secretase, 37 amino acid peptide (VLSSQQFLHRGHQPPPEMAGHSLASSHRNSMIPSAAT) also known being produced in the (non-patent document 11).
However, such a peptide to Alzheimer's disease is the idea of control agent, the present finding, is assumed for the state of the art is difficult, and thus in no way has been reported.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • HOKKAIDO UNIV
  • 発明者(英語)
  • INOUE, Tsuyoshi
  • SUZUKI, Toshiharu
  • BAN, Saori
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN TD TG

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